In a phase II trial (SALV-ENZA) reported in the Journal of Clinical Oncology, Phuoc T. Tran, MD, PhD, and colleagues found that the addition of enzalutamide to salvage radiotherapy improved freedom from prostate-specific antigen (PSA) progression in patients with biochemically recurrent prostate cancer after radical prostatectomy who were not receiving androgen-deprivation therapy.
Phuoc T. Tran, MD, PhD
Study Details
In the U.S. multicenter double-blind trial, 86 patients were randomly assigned between April 2015 and February 2020 to receive enzalutamide at 160 mg (n = 43) or placebo (n = 43) once daily for 180 days. Salvage radiotherapy was initiated on day 61 and ended on day 120 and was given as external-beam radiation (66.6–70.2 Gy in 1.8 Gy fractions 5 days per week for 37–39 fractions) administered to the prostate bed (no pelvic nodes). The primary endpoint was freedom from PSA progression in the intention-to-treat population.
Freedom From PSA Progression
Median follow-up was 34 months (range = 0–52 months). At study closure, PSA progression had occurred in 10 patients in the enzalutamide group (23%; at 9–39 months after random assignment) vs 18 patients in the placebo group (42%, at 4–33 months after random assignment), yielding a hazard ratio (HR) of 0.42 (95% confidence interval [CI] = 0.19–0.92, P = .031) on stratified analysis including surgical margin status, Gleason sum, and baseline PSA. Freedom from PSA progression at 2 years was 84% vs 66% (P = .027).
Subgroup analyses indicated differential benefit of enzalutamide among patients with pT3 disease (n = 28 in both groups; HR = 0.22, 95% CI = 0.07–0.69) vs pT2 disease (14 in enzalutamide group vs 15 in placebo group; HR = 1.54, 95% CI = 0.4–-5.47, P = .019 for interaction) and among those with R1 resection (21 vs 22 patients; HR = 0.14, 95% CI = 0.03–0.64) vs R0 resection (22 vs 21 patients; HR = 1.00, 95% CI = 0.36–2.76, P = .023 for interaction).
No documented local recurrences and only one metastasis event were observed at the time of analysis, prohibiting analysis of these secondary endpoints.
KEY POINTS
- The addition of enzalutamide to salvage radiotherapy was associated with significantly reduced risk of PSA progression.
- Differential benefit of enzalutamide was observed among patients with pT3 vs pT2 disease and with R1 vs R0 resection.
Adverse Events
Grade 3 adverse events occurred in three patients in the enzalutamide group and seven in the placebo group; no grade 4 events were reported. The most common grade 1 or 2 adverse events in the enzalutamide group were fatigue (65% vs 53% in placebo group) and urinary frequency (40% vs 49% in placebo group). Grade 1 or 2 breast/nipple pain (26% vs 0%, P = .001) and nausea (19% vs 0%, P =.01) were significantly more common in the enzalutamide group.
In the enzalutamide group, one patient died from developing pancreatic cancer and one died from unknown causes. In the placebo group, two patients developed other cancers (glioblastoma multiforme and squamous cell carcinoma of the tonsil), with no deaths reported.
The investigators concluded, “Salvage radiotherapy plus enzalutamide monotherapy for 6 months in men with PSA-recurrent high-risk prostate cancer after radical prostatectomy is safe and delays PSA progression relative to salvage radiotherapy alone. The impact of enzalutamide on distant metastasis or survival is unknown at this time.”
Emmanuel S. Antonarakis, MD, of the Department of Medicine, University of Minnesota, Minneapolis, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Astellas Pharma Global Development, Inc, and Pfizer, Inc. For full disclosures of the study authors, visit ascopubs.org.
